MelanomaPhase 2NCT01619774
An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor
A Phase 2 study testing GSK2118436 and GSK1120212 in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if the combination of 2 drugs dabrafenib and trametinib can help to control melanoma that has or has not spread to the brain. The safety of this drug combination will also be studied. Dabrafenib is designed to block the mutated BRAF protein. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- GSK2118436 and GSK1120212
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Patients must have histologically or cytologically confirmed Stage IV or recurrent or unresectable Stage III melanoma.
- BRAF mutation-positive melanoma (i.e., V600E, V600K or V600D)
- For Cohort A, patients must have easily accessible tumor for a mandatory biopsy. This is not required for patients enrolled on Cohort B.
- Patients must have measurable disease, defined by RECIST 1.1
- Patients must have tumor lesions which is refractory or resistant to a selective BRAF inhibitor (RO5185426 or GSK2118436).
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- Age >/= 16 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have organ and marrow function as defined below: · absolute neutrophil count >/= 1,500/mcL · platelets >/= 75,000/mcL · total bilirubin </= 1.5 × institutional upper limit of normal: no restriction to serum bilirubin level if Gilbert's syndrome is diagnosed or suspected · AST(SGOT)/ALT(SGPT) </= 2.5 × institutional upper limit of normal, (</= 3x upper limit of normal for AST and ALT for those subjects with liver metastasis) · creatinine </= 1.3 × institutional upper limit of normal OR · creatinine clearance >/= 60 mL/min/1.73 m2 for patients with creatinine levels above 1.3 X institutional upper limit of normal.
- Ability to understand and the willingness to sign a written informed consent document.
- For Cohort B, patients must have at least 1 measureable parenchymal brain metastasis of at least 10 mm in the greatest diameter and no greater than 40 mm diameter. There must be at least one parenchymal brain metastasis that has not received any previous locally-directed treatment (i.e. surgery or radiation), or that has progressed after prior treatment for the brain metastases (i.e. surgery or radiation).
- Male subjects must agree to use contraception, this criterion must be followed from the time of the first dose of study medication until 4 weeks after the last dose of study medication. However, it is advised that contraception be used for a total of 16 weeks following the last dose (based on the lifecycle of sperm).
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use contraception if they wish to continue their HRT during the study. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- (cont' from Inclusion #12) • Child-bearing potential and agrees to use one of the contraception methods listed in Section 7.1.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 4 weeks after the last dose of study medication, and must have a negative serum pregnancy test within 14 days prior to the start of dosing. Note: Oral contraceptives are not reliable due to potential drug-drug interaction.
Who cannot join
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) except a selective RAF inhibitor.
- Patients must not have previously received a selective BRAF inhibitor (RO5185426, GSK2118436) and a selective MEK inhibitor (AZD6244, GSK1120212) concurrently.
- Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of study drug administration, other than BRAF inhibitor--at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and the first dose of study drug. However, there is no required washout period for any BRAF inhibitors at least until the baseline biopsy is performed.
- Current use of a prohibited medication or requires any of these medications during treatment with study drug.
- Any major surgery, within the last 3 weeks. Radiotherapy, or immunotherapy within the last 2 weeks.
- Unresolved toxicity greater than NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Grade 1 from previous anti-cancer therapy except alopecia and peripheral neuropathy, for which </= grade 2 toxicity is allowed to participate.
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- Presence of rheumatoid arthritis.
- History of retinal vein occlusion or central serous retinopathy, or predisposing factors to retinal vein occlusion or central serous retinopathy (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- Brain Metastases a. For cohort A, patients will be excluded if they have brain metastases, unless they have been previously treated brain metastases with surgery or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size) for at least 4 weeks with MRI scans using contrast prior to Day 1. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs and/or steroids to control symptoms/signs of brain metastases. Patients previously treated with whole brain radiation therapy must have confirmed stable disease for at least 12 weeks prior to starting treatment. However, untreated asymptomatic brain metastasis less than 10 mm will be allowed if no steroid and anti-epileptic drugs are used.
- 10 (con't) b. For cohort B, patients may not have any evidence of leptomeningeal disease. Use of corticosteroids is permitted as long as the dose of steroids required for symptom control has been stable or decreasing for at least 3 weeks prior to the first dose of study treatment.
- History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months.
- Corrected QT interval (QTc) >/= 480 msec (>/= 500 msec for subjects with Bundle Branch Block).
- Uncontrolled arrhythmias. • Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are eligible.
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered on study if deemed not clinically significant)
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients. NOTE: To date there are no known FDA approved drugs chemically related to GSK2118436 or GSK1120212.
- Pregnant or lactating female.
- Unwillingness or inability to follow the procedures required in the protocol.
- Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
- Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
The goal of this clinical research study is to learn if the combination of 2 drugs dabrafenib and trametinib can help to control melanoma that has or has not spread to the brain. The safety of this drug combination will also be studied.
Dabrafenib is designed to block the mutated BRAF protein. This mutation is only found in moles of the skin and in melanoma cells. By blocking the protein, the drug may slow the growth of or kill cancer cells that have the protein.
Trametinib is designed to block certain proteins that cause cancer cells to grow and multiply. This may cause the cancer cells to die.
Read the detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take both dabrafenib and trametinib together.
You will take 1 capsule of trametinib by mouth once a day. You will take 2 capsules of dabrafenib by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart - a total of 4 capsules a day). If you experience severe side effects, your doctor or the research team may lower the dose of the drug(s).
You should take the study drugs with about 1 cup (8 ounces) of room-temperature water. You should not eat or drink anything besides water for at least 1 hour before and 2 hours after you take the study drugs.
You will be given a study drug diary to record the times and doses that you take the study drugs. You should bring the diary to each study visit.
Study Visits:
On Day 1 of Cycle 1:
- Your medical history will be recorded, including any symptoms you may be having. (if it was not recorded in the previous 7 days)
- Your weight, vital signs, and performance status will be recorded.
- You will have a physical exam (if one was not performed in the previous 7 days).
- Blood (about 2 teaspoons) will be collected for routine tests (if this was not performed in the previous 7 days).
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
- You will have a blood draw this visit for research purposes.
At some point between Day 4-10 of Cycle 1, you will have the same kind of biopsy that you had at screening. Your doctor and/or the study team will discuss this with you.
On Days 8 of Cycle 1:
- Your weight, vital signs, and performance status will be recorded.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will be asked about any drugs or herbal supplements that you may be taking.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
On Day 15 of Cycle 1:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- You will have an ECG.
- Blood (about 2 teaspoons) will be collected for routine tests.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
- If the disease has spread to the brain and your doctor thinks it is needed, you will have an MRI of the brain.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- Blood (about 2 teaspoons) will be collected for routine tests.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects
- Blood (about 4 tablespoons) will be drawn for biomarker testing on day 1 of Cycle 2 and 4. If your disease worsens, blood (about 4 tablespoons) will also be drawn at that time.
Every 8 weeks (2 cycles) from the time of the start of the treatment, you will have an x-ray, a CT scan, an MRI scan, a skin exam, and/or a bone scan to check the status of the disease.
Every 12 weeks, you will have an ECHO performed.
If at any point during the study you have any symptoms or signs of a serious skin, eye, or heart side effect, you may be referred to a dermatologist or an ophthalmologist, or you may have an ECG and ECHO to check your heart's health.
Length of Study:
You may continue taking the study drugs for as long as the study doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, you start having other health problems, or intolerable side effects occur.
Your participation on the study will be over once you have completed the end-of-study visit.
End-of-Study Visit:
You will have an end-of-study visit within 4 weeks after your last dose of study drugs. The following tests and procedures will be performed:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- You will have an ECG.
- Blood (about 2 teaspoons) will be collected for routine tests. You will have an x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, and/or bone scan to check the status of the disease if you are taken off the study for any other reason than the disease getting worse.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will have the same kind of mandatory biopsy that you did at screening. You may be allowed to continue receiving the study drugs until the time of this biopsy (up to 2 days) even if the disease is not showing a response to the study drugs. Your doctor and/or the study team will discuss this with you.
Survival Follow-Up:
After you stop taking study drug, you will be followed approximately every 3 months (either clinic visit or contact by phone or letter) for 5 years or until death. If you are called, the call will last about 5 minutes.
This is an investigational study. This is an investigational study. Both trametinib and dabrafenib are FDA approved and commercially available for the treatment of certain types of melanoma. Their use together in this study is investigational.
Up to 45 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Melanoma
- Being tested
- GSK2118436, GSK1120212
- Keywords
- Melanoma, Metastatic melanoma, Refractory or Resistant to BRAF Inhibitor, Advanced melanoma, GSK2118436, GSK1120212
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2118436Drug
Starting dose 150 mg by mouth twice a day.
GSK1120212Drug
2 mg by mouth daily.
| Study group | Role | What they receive |
|---|---|---|
| GSK2118436 + GSK1120212 | Experimental | GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart). Receives: Drug: GSK2118436; Drug: GSK1120212 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall response rate defined as percentage of subjects with a confirmed complete response (CR) or a partial response (PR) at any time as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Clinical responses will be evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks).
Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
Measured: Evaluation every 8 weeks (2 cycles) up to 12 months
Number of Participants by Response
Clinical responses evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
Measured: Evaluation every 8 weeks (2 cycles) up to 12 months
Secondary outcomes (1)
Progression-Free Survival (PFS)
Duration of response defined for subjects with a confirmed complete response (CR) or partial response (PR), as time from the first documented evidence of a CR or PR until the first documented disease progression or death due to any cause. Progression free survival (PFS) estimated and summarized using the method of Kaplan and Meier.
Measured: Evaluation every 8 weeks (2 cycles) up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2012 (estimated)
- Study startSep 2012
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Prevention Research Institute of Texas, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Michael Davies, MD, PHD, BA, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01619774
- Sponsor's protocol ID
- 2011-0579
- Other IDs
- NCI-2012-01222, RP120505
- Status last verified
- Oct 2016
- First submitted
- 12 Jun 2012
- Last updated
- 12 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Chen G, McQuade JL, Panka DJ, Hudgens CW, Amin-Mansour A, Mu XJ, Bahl S, Jane-Valbuena J, Wani KM, Reuben A, Creasy CA, Jiang H, Cooper ZA, Roszik J, Bassett RL Jr, Joon AY, Simpson LM, Mouton RD, Glitza IC, Patel SP, Hwu WJ, Amaria RN, Diab A, Hwu P, Lazar AJ, Wargo JA, Garraway LA, Tetzlaff MT, Sullivan RJ, Kim KB, Davies MA. Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial. JAMA Oncol. 2016 Aug 1;2(8):1056-64. doi: 10.1001/jamaoncol.2016.0509.
PubMed 27124486
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor
- ClinicalTrials.gov ID
- NCT01619774
- Acronym / sponsor ID
- 2011-0579
- Conditions
- Melanoma
- Keywords
- Melanoma, Metastatic melanoma, Refractory or Resistant to BRAF Inhibitor, Advanced melanoma, GSK2118436, GSK1120212
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Cancer Prevention Research Institute of Texas, GlaxoSmithKline
- Study start
- Sep 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 14 Jun 2012 (estimated)
- Results
- Posted 12 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if the combination of 2 drugs dabrafenib and trametinib can help to control melanoma that has or has not spread to the brain. The safety of this drug combination will also be studied.
Dabrafenib is designed to block the mutated BRAF protein. This mutation is only found in moles of the skin and in melanoma cells. By blocking the protein, the drug may slow the growth of or kill cancer cells that have the protein.
Trametinib is designed to block certain proteins that cause cancer cells to grow and multiply. This may cause the cancer cells to die.
Detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take both dabrafenib and trametinib together.
You will take 1 capsule of trametinib by mouth once a day. You will take 2 capsules of dabrafenib by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart - a total of 4 capsules a day). If you experience severe side effects, your doctor or the research team may lower the dose of the drug(s).
You should take the study drugs with about 1 cup (8 ounces) of room-temperature water. You should not eat or drink anything besides water for at least 1 hour before and 2 hours after you take the study drugs.
You will be given a study drug diary to record the times and doses that you take the study drugs. You should bring the diary to each study visit.
Study Visits:
On Day 1 of Cycle 1:
- Your medical history will be recorded, including any symptoms you may be having. (if it was not recorded in the previous 7 days)
- Your weight, vital signs, and performance status will be recorded.
- You will have a physical exam (if one was not performed in the previous 7 days).
- Blood (about 2 teaspoons) will be collected for routine tests (if this was not performed in the previous 7 days).
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
- You will have a blood draw this visit for research purposes.
At some point between Day 4-10 of Cycle 1, you will have the same kind of biopsy that you had at screening. Your doctor and/or the study team will discuss this with you.
On Days 8 of Cycle 1:
- Your weight, vital signs, and performance status will be recorded.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will be asked about any drugs or herbal supplements that you may be taking.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
On Day 15 of Cycle 1:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- You will have an ECG.
- Blood (about 2 teaspoons) will be collected for routine tests.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.
- If the disease has spread to the brain and your doctor thinks it is needed, you will have an MRI of the brain.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- Blood (about 2 teaspoons) will be collected for routine tests.
- You will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects
- Blood (about 4 tablespoons) will be drawn for biomarker testing on day 1 of Cycle 2 and 4. If your disease worsens, blood (about 4 tablespoons) will also be drawn at that time.
Every 8 weeks (2 cycles) from the time of the start of the treatment, you will have an x-ray, a CT scan, an MRI scan, a skin exam, and/or a bone scan to check the status of the disease.
Every 12 weeks, you will have an ECHO performed.
If at any point during the study you have any symptoms or signs of a serious skin, eye, or heart side effect, you may be referred to a dermatologist or an ophthalmologist, or you may have an ECG and ECHO to check your heart's health.
Length of Study:
You may continue taking the study drugs for as long as the study doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, you start having other health problems, or intolerable side effects occur.
Your participation on the study will be over once you have completed the end-of-study visit.
End-of-Study Visit:
You will have an end-of-study visit within 4 weeks after your last dose of study drugs. The following tests and procedures will be performed:
- You will have a physical exam.
- Your weight, vital signs, and performance status will be recorded.
- You will have an ECG.
- Blood (about 2 teaspoons) will be collected for routine tests. You will have an x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, and/or bone scan to check the status of the disease if you are taken off the study for any other reason than the disease getting worse.
- Blood (about 4 tablespoons) will be drawn for biomarker testing.
- You will have the same kind of mandatory biopsy that you did at screening. You may be allowed to continue receiving the study drugs until the time of this biopsy (up to 2 days) even if the disease is not showing a response to the study drugs. Your doctor and/or the study team will discuss this with you.
Survival Follow-Up:
After you stop taking study drug, you will be followed approximately every 3 months (either clinic visit or contact by phone or letter) for 5 years or until death. If you are called, the call will last about 5 minutes.
This is an investigational study. This is an investigational study. Both trametinib and dabrafenib are FDA approved and commercially available for the treatment of certain types of melanoma. Their use together in this study is investigational.
Up to 45 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2118436 + GSK1120212 | Experimental | Drug: GSK2118436, Drug: GSK1120212GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Patients must have histologically or cytologically confirmed Stage IV or recurrent or unresectable Stage III melanoma.
- BRAF mutation-positive melanoma (i.e., V600E, V600K or V600D)
- For Cohort A, patients must have easily accessible tumor for a mandatory biopsy. This is not required for patients enrolled on Cohort B.
- Patients must have measurable disease, defined by RECIST 1.1
Key exclusion criteria (21 listed)
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) except a selective RAF inhibitor.
- Patients must not have previously received a selective BRAF inhibitor (RO5185426, GSK2118436) and a selective MEK inhibitor (AZD6244, GSK1120212) concurrently.
- Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of study drug administration, other than BRAF inhibitor--at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and the first dose of study drug. However, there is no required washout period for any BRAF inhibitors at least until the baseline biopsy is performed.
- Current use of a prohibited medication or requires any of these medications during treatment with study drug.
- Any major surgery, within the last 3 weeks. Radiotherapy, or immunotherapy within the last 2 weeks.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2118436Starting dose 150 mg by mouth twice a day. | Drug | GSK2118436 + GSK1120212 |
| GSK11202122 mg by mouth daily. | Drug | GSK2118436 + GSK1120212 |
Primary outcome
Overall Response Rate (ORR)
Time frame: Evaluation every 8 weeks (2 cycles) up to 12 months
Overall response rate defined as percentage of subjects with a confirmed complete response (CR) or a partial response (PR) at any time as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Clinical responses will be evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
Number of Participants by Response
Time frame: Evaluation every 8 weeks (2 cycles) up to 12 months
Clinical responses evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): >20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of >5 mm; appearance of 1 or > new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.
1 secondary outcome
Progression-Free Survival (PFS)
Time frame: Evaluation every 8 weeks (2 cycles) up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27124486Chen G, McQuade JL, Panka DJ, Hudgens CW, Amin-Mansour A, Mu XJ, Bahl S, Jane-Valbuena J, Wani KM, Reuben A, Creasy CA, Jiang H, Cooper ZA, Roszik J, Bassett RL Jr, Joon AY, Simpson LM, Mouton RD, Glitza IC, Patel SP, Hwu WJ, Amaria RN, Diab A, Hwu P, Lazar AJ, Wargo JA, Garraway LA, Tetzlaff MT, Sullivan RJ, Kim KB, Davies MA. Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial. JAMA Oncol. 2016 Aug 1;2(8):1056-64. doi: 10.1001/jamaoncol.2016.0509.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Davies, MD, PHD, BA principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2118436 and GSK1120212 in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Evaluation every 8 weeks (2 cycles) up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01619774, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2016.